3-128480473-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032638.5(GATA2):c.*546C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 238,984 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (83 hom., cov: 33)
  • Exomes 𝑓: 0.043 (99 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.20

Genes affected

GATA2 (HGNC:4171): (GATA binding protein 2) This gene encodes a member of the GATA family of zinc-finger transcription factors that are named for the consensus nucleotide sequence they bind in the promoter regions of target genes. The encoded protein plays an essential role in regulating transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-128480473-G-A is Benign according to our data. Variant chr3-128480473-G-A is described in ClinVar as [Benign]. Clinvar id is 343120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.*546C>T		3_prime_UTR_variant	7/7	ENST00000487848.6
GATA2	NM_032638.5	c.*546C>T		3_prime_UTR_variant	6/6	ENST00000341105.7
GATA2	NM_001145662.1	c.*546C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.*546C>T		3_prime_UTR_variant	6/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.*546C>T		3_prime_UTR_variant	7/7	1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4660 AN: 152210 Hom.: 82 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0803

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.00762

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0425 AC: 3685 AN: 86656 Hom.: 99 Cov.: 0 AF XY: 0.0421 AC XY: 1688 AN XY: 40138

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0705

Gnomad4 ASJ exome AF: 0.0370

Gnomad4 EAS exome AF: 0.0806

Gnomad4 SAS exome AF: 0.0208

Gnomad4 FIN exome AF: 0.0117

Gnomad4 NFE exome AF: 0.0368

Gnomad4 OTH exome AF: 0.0371

GnomAD4 genome AF: 0.0306 AC: 4663 AN: 152328 Hom.: 83 Cov.: 33 AF XY: 0.0304 AC XY: 2266 AN XY: 74486

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.0801

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.00762

Gnomad4 NFE AF: 0.0359

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0330 Hom.: 15

Bravo AF: 0.0346

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.095
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs45463801; hg19: chr3-128199316;